Tissue engineering has recently focused on biomimetic matrices, usually polymer hydrogels, that include multiple layers with distinct structures and chemical components. (see, P. X. Ma, Adv. Drug Deliv. Rev. 2008, 60, 184; K. Y. Lee, et al., Chem. Rev. 2001, 101, 1869; A. Khademhosseini, et al., Biomaterials 2007, 28, 5087).
Current methods of fabricating such matrices are complex or expensive to implement and often produce mechanical weaknesses between layers. (see, E. S. Place, et al., Nat. Mater. 2009, 8, 457) Thus, an adaptable, facile, and economical multilayer polymer fabrication technique that produces continuous interfaces between layers is needed.
Existing strategies allow for construction of multiphase scaffolds with varying degrees of complexity. Multiphase biopolymer-based hydrogel matrices have been previously fabricated by additive photopatterning, (see, V. A. Liu, et al., Biomed. Microdevices 2002, 4, 257; J. H. Elisseeff, et al., Tissue Eng.g 2007, 13, 405; L. M. Weber, C. Y. Cheung, K. S. Anseth, Cell Transplantation 2008, 16, 1049), laser scanning lithography (see, M. S. Hahn, et al., Adv. Materials 2005, 17, 2939), printing (see, T. Boland, et al., Biotechnology J. 2006, 1, 910), sequential functionalization (see, S. Kizilel, et al., Biomaterials 2006, 27, 1209), and freeze-drying (see, B. A. Harley, et al., J. Biomed. Mater. Res. A 2010, 92, 1078; S. Varghese, et al., J. Mater. Chem. 2010, 20, 345).
Additionally, spatial control of chemical or mechanical gradients has been achieved using gradient makers (see, K. Chatterjee, et al., Biomaterials 2010, 31, 5051), microfluidics (see, S. Cosson, et al., Adv. Funct. Materials 2009, 19, 3411; J. He, et al., Adv. Funct. Materials 2010, 20, 131; M. P. Cuchiara, et al., Biomaterials 2010, 31, 5491), and centrifugation (see, J. L. Roam, et al., Biomaterials 2010, 31, 8642). Another approach is to attach layers after fabrication (see, K. S. Straky, et al., Adv. Materials 2009, 21, 4148; J. P. Gleghorn, et al., J. Biomed. Materials Res.-A 2008, 85, 611).
However, these techniques may not be widely adopted because they require sophisticated instrumentation and/or technical proficiency.